The M5 (m5) receptor subtype: Fact or fiction?
The M5 (m5) receptor subtype: Fact or fiction?
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DOI：
10.1016/s0024-3205(97)00054-4
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发表时间：
1997-02-21
期刊：
影响因子：
6.1
通讯作者：
Flynn, DD
中科院分区：
文献类型：
--
作者：
Reever, CM;FerrariDiLeo, G;Flynn, DD
与毒蕈碱受体的其他亚型相比，人们对 M5 (m5)* 受体亚型的结合特性、位置、机制和生理功能知之甚少。由于缺乏 m5 选择性配体或抗体以及主要内源表达 m5 受体亚型的来源，m5 受体的研究受到阻碍。我们开发了一种药理学标记策略，使用非选择性毒蕈碱拮抗剂[H-3]NMS，在毒蕈碱拮抗剂和绿曼巴毒液毒素存在下封闭m1-m4受体亚型，选择性标记m5受体亚型。这种 m5 选择性标记方法，以及为其他四种受体亚型开发的方法，首次允许比较大脑中五种毒蕈碱受体亚型的相对表达水平和解剖定位。 m5受体的分布特征与其他四种亚型不同，并且富含于皮质外层、海马体、尾壳核、嗅结节和伏隔核的特定亚区。这些研究还表明，m5 受体蛋白表达水平明显高于先前原位杂交和免疫沉淀研究的预期，且分布范围更广。总而言之，这些结果表明 m5 受体亚型在调节大脑中乙酰胆碱的作用方面具有独特且潜在的重要生理作用。
By comparison to the other subtypes of muscarinic receptors, very little is known about the binding properties, locations, mechanisms and physiological functions of the M5 (m5)* receptor subtype. Studies of the m5 receptor have been hampered by the lack of m5-selective ligands or antibodies and a source that endogenously expresses predominantly the m5 receptor subtype. We have developed a pharmacological labeling strategy using the non-selective muscarinic antagonist [H-3]NMS, in the presence of muscarinic antagonists and toxins in green mamba venom to occlude the m1-m4 receptor subtypes, to selectively label the m5 receptor subtype. This m5-selective labeling approach, along with those developed for the other four receptor subtypes, has permitted for the first time a comparison of the relative expression levels and anatomical localizations of the five muscarinic receptor subtypes in the brain. The distribution profile of the m5 receptor is distinct from the other four subtypes and is enriched in the outer layers of the cortex, specific subfields of the hippocampus, caudate putamen, olfactory tubercle and nucleus accumbens. These studies have also demonstrated that the levels of m5 receptor protein expression are apparently higher and more widespread than anticipated from previous in situ hybridization and immunoprecipitation studies. Taken together, the results suggest a unique and potentially physiologically important role for the m5 receptor subtype in modulating the actions of acetylcholine in the brain.